Seminars in Cancer Biology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Biomolecules, Год журнала: 2022, Номер 13(1), С. 36 - 36
Опубликована: Дек. 24, 2022
Cadmium (Cd) is a toxic metal for the human organism and all ecosystems. Cd naturally found at low levels; however, higher amounts of in environment result from activities as it spreads into air water form micropollutants consequence industrial processes, pollution, waste incineration, electronic recycling. The body has limited ability to respond exposure since does not undergo metabolic degradation less species only poorly excreted. extremely long biological half-life essentially makes cumulative toxin; chronic causes harmful effects stored organs. present paper considers potential health concerns due environmental cadmium. Exposure compounds primarily associated with an elevated risk lung, kidney, prostate, pancreatic cancer. also been linked cancers breast, urinary system, bladder. multiple mechanisms Cd-induced carcinogenesis include oxidative stress inhibition antioxidant enzymes, promotion lipid peroxidation, interference DNA repair systems. Cd2+ can replace essential ions, including redox-active ones. A total 12 cancer types specific genes coding Cd-metalloproteome were identified this work. In addition, we summarize proper treatments poisoning, based on use selected detoxifying agents chelators, preventive approaches counteract its exposure.
Язык: Английский
Процитировано
147
Biomolecules, Год журнала: 2022, Номер 12(3), С. 360 - 360
Опубликована: Фев. 24, 2022
More than one and a half centuries ago, adverse human health effects were reported after use of cadmium-containing silver polishing agent. Long-term cadmium exposure gives rise to kidney or bone disease, reproductive toxicity cancer in animals humans. At present, high exposures occur small-scale mining, underlining the need for preventive measures. This is particularly urgent view growing demand minerals metals global climate change mitigation. review deals with specific part toxicology that important understanding when toxic appear and, thus, crucial risk assessment. The discovery low-molecular-weight protein metallothionein (MT) 1957 was an milestone because, this binds cadmium, it modifies cellular toxicity. present authors contributed evidence 1970s concerning binding MT synthesis tissues. We showed tissues prevented some effects, but can increase transport kidneys. Special studies importance Cd/Zn ratio expression also developed models toxicokinetics based on our MT-related findings. model combined estimates tissue levels giving toxicity, made possible calculate expected risks relation exposure. Other scientists these further international organizations have successfully used amended recent publications. Our contributions decades included humans biomarkers showing gene lymphocytes autoantibodies Cd-related cadmium-exposed population groups. In study impact zinc status dysfunction group, low good poor. summarizes assessment context calls its application order improve measures against animals.
Язык: Английский
Процитировано
138
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Янв. 3, 2024
Abstract Zinc metabolism at the cellular level is critical for many biological processes in body. A key observation disruption of homeostasis, often coinciding with disease progression. As an essential factor maintaining equilibrium, zinc has been increasingly spotlighted context development. Extensive research suggests zinc’s involvement promoting malignancy and invasion cancer cells, despite its low tissue concentration. This led to a growing body literature investigating metabolism, particularly functions transporters storage mechanisms during transportation under control two major transporter families: SLC30 (ZnT) excretion SLC39 (ZIP) intake. Additionally, this element predominantly mediated by metallothioneins (MTs). review consolidates knowledge on signaling underscores potential molecular pathways linking progression, special focus cancer. We also compile summary clinical trials involving ions. Given main localization cell membrane, targeted therapies, including small molecules monoclonal antibodies, offers promising avenues future exploration.
Язык: Английский
Процитировано
88
Chemistry and Ecology, Год журнала: 2024, Номер 40(3), С. 322 - 349
Опубликована: Янв. 22, 2024
Heavy metals, pervasive in the environment due to natural processes and human activities, pose substantial threats ecosystems health. This study aims delve into sources, contamination pathways waters, subsequent bioaccumulation of heavy metals across various organisms. The overview encompasses an exploration environmental persistence, dynamics, ecotoxicological impacts these metals. Methodologically, this research undertakes a comprehensive review synthesizing existing literature studies on metal contamination, mechanisms, ecotoxicity. Key findings highlight protracted persistence perpetuating significant ecological balance well-being. Notably, transfer through food chains culminates their diverse organisms, raising concerns about potential toxicity, including exposure. discussion underscores imperative nature assessing pollution its ramifications Emphasizing essential role bioindicators biomarkers, article elucidates significance evaluating metal-induced stressors impact both biota populations. contributes nuanced understanding advocating for proactive measures monitoring mitigating deleterious effects
Язык: Английский
Процитировано
80
Archives of Toxicology, Год журнала: 2023, Номер 97(2), С. 329 - 358
Опубликована: Янв. 2, 2023
Язык: Английский
Процитировано
61
EFSA Journal, Год журнала: 2023, Номер 21(1)
Опубликована: Янв. 1, 2023
Copper is an essential micronutrient and also a regulated product used in organic conventional farming pest management. Both deficiency excessive exposure to copper can have adverse health effects. In this Scientific Opinion, the EFSA 2021 harmonised approach for establishing health-based guidance values (HBGVs) substances that are products nutrients was resolve divergent existing HBGVs copper. The tightly homeostasis prevents toxicity manifestation short term, but development of chronic dependent on its tissue retention. Evidence from Wilson disease suggests hepatic retention indicative potential future possibly sudden onset under conditions continuous intake. Hence, emphasis placed as early marker relationships between (a) body, particularly liver, (b) concentrations evidence were examined. Committee (SC) concludes no expected occur with intake 5 mg/day established Acceptable Daily Intake (ADI) 0.07 mg/kg bw. A refined dietary assessment performed, assessing contribution non-dietary sources. Background levels significant source use plant protection (PPP), food feed additives or fertilisers negligible. PPPs contributes accumulation soil. Infant formula follow-on important contributors infants toddlers. Contribution non-oral sources Dietary total does not exceed HBGV adolescents, adults, elderly very elderly. Neither nor effects estimated children due higher nutrient requirements related growth.
Язык: Английский
Процитировано
42
Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(8)
Опубликована: Дек. 22, 2022
Zinc homeostatic medicine is of great potential for cancer chemo-immunotherapy; however, there are few reports on antitumor compounds that can trigger Zn2+ -mediated immune responses. In this work, we developed a novel cyclometalated PtIV -terthiophene complex, Pt3, not only induces DNA damage and cellular metabolism dysregulation, but also disrupts zinc homeostasis as indicated by the abnormal transcriptional level regulatory proteins, excess accumulation in cytoplasm, down-regulation metallothioneins (MTs), which further caused redox imbalance. The simultaneous disruption response to Pt3 treatment activated gasdermin-D mediated pyroptosis accompanied cytoskeleton remodeling, thus releasing pro-inflammatory cytokines promote dendritic cell (DC) maturation T tumor-infiltration, eventually eliminating both primary distant tumors vivo. As far know, first metal complex regulate activate immunity.
Язык: Английский
Процитировано
51
European Journal of Neuroscience, Год журнала: 2024, Номер 60(1), С. 3505 - 3543
Опубликована: Май 15, 2024
Abstract Copper is a critical trace element in biological systems due the vast number of essential enzymes that require metal as cofactor, including cytochrome c oxidase, superoxide dismutase and dopamine‐ β ‐hydroxylase. Due its key role oxidative metabolism, antioxidant defence neurotransmitter synthesis, copper particularly important for neuronal development proper function. Moreover, increasing evidence suggests also serves functions synaptic network activity, regulation circadian rhythms, arousal. However, it to note because copper's ability redox cycle generate reactive species, cellular levels must be tightly regulated meet needs while avoiding copper‐induced stress. Therefore, intricate system transporters, exporters, chaperones trafficking proteins function properly coordinate fashion. Indeed, disorders metabolism such Menkes disease Wilson disease, well diseases linked dysfunction copper‐requiring enzymes, SOD1‐linked amyotrophic lateral sclerosis, demonstrate dramatic neurological consequences altered homeostasis. In this review, we explore physiological importance nervous pathologies related improper handling.
Язык: Английский
Процитировано
12
APOPTOSIS, Год журнала: 2024, Номер 29(9-10), С. 1330 - 1360
Опубликована: Июль 16, 2024
Язык: Английский
Процитировано
12
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Янв. 6, 2024
Abstract Pancreatic β-cells respond to metabolic stress by upregulating insulin secretion, however the underlying mechanisms remain unclear. Here we show, in from overweight humans without diabetes and mice fed a high-fat diet for 2 days, exocytosis secretion are enhanced increased Ca 2+ influx. RNA-seq of sorted suggests altered pathways early following high fat diet, where find basal oxygen consumption proton leak, but more reduced cytosolic redox state. Increased β-cell after 2-day is dependent on this intracellular state requires sentrin-specific SUMO-protease-1. Mice with either pancreas- or β-cell-specific deletion fail up-regulate become rapidly glucose intolerant diet. Mechanistically, redox-sensing SUMO-protease thiol group at C535 which together Zn + -binding suppresses protease activity unrestrained exocytosis, increases enzyme sensitivity regulation signals.
Язык: Английский
Процитировано
11